Evolutionary cell biology
The idea that evolution can shed light on how cells work — and why they work the way they do — makes a lot of sense. Mike Lynch and colleagues wrote a nice perspective that you can read here.
I was always intrigued by Sophie Kahn’s early discovery — during the course of work on the genetics of wrinkly spreaders — of mreB mutants that could no longer colonise the air-liquid interface. Several things about this discovery stuck in my mind, not least of which the fact that mreB mutants of E. coli are lethal, but also knowledge that mreB cells are spherical.
In the late 2000s Monica Gerth was finishing a post doc and was interested in a new avenue of research and so it was suggested that she make a clean mreB deletion mutant of SBW25, check its phenotype (spherical cells) and assess its fitness. Assuming fitness was much reduced (it was) and cells were spherical (they were), then the suggestion was that she propagate the mutant in laboratory media to see whether selection could compensate for the fitness cost associated with inability to correctly position the division septum. This she did.
Monica found fitness was rapidly restored, while the cells remained spherical. More about this project from the link below, but the work showed how powerful this kind of evolutionary approach to cell biology can be. It becomes especially powerful when coupled with time-resolved microscopy where we enjoy super collaboration with Nicolas Desprat. Two of his movies are below. Both show growth of the ∆mreB mutant. The left shows “bridges” between cells. If you watch carefully you can see that bridges even form between non-daughter cells. We don’t understand this, but if you are intrigued, then contact us. The right image has the same cells but this time with blue lines positioned by an algorithm that define the long axis (yes, the ∆mreB mutant produces cells that still have a long axis even though this is not perceptible by the eye). Interestingly the division plane forms perpendicular to the long axis.
At the present time Malavika Venu with Dave Rogers‘s help is fusing the cell cycle (division inhibitor) gene minC to gfp to see whether we can capture oscillations and observe what happens in the mreB mutant background.
Given the range of well-studied components involved in determination of cell size / shape and paucity of knowledge concerning why such components function as they do, there exist excellent opportunities to deliver new insight into fundamental problems such as how rate of wall synthesis is coupled to rate of cell division; how chromosome segregation is linked to the cell cycle; how cell size is regulated. As always, there are just too many interesting possibilities.